Cystic fibrosis is one of the most common genetic diseases which leads to early death; it is present in one out of 1500-2000 Caucasian infants. Although inheritance follows an autosomal recessive pattern, there is no currently reliable method for identifying carriers of this condition; in addition, the basic biochemical defect has yet to be elucidated. In this proposal we present preliminary observations utilizing fibroblasts in vitro which show that cells derived from cystic fibrosis individuals are significantly more resistant than cells derived from normal individuals to the cytotoxic effects of the cardiac glycoside, ouabain, under a specific set of conditions. It is the object of this proposal to examine in depth the reasons for this preliminary observation at the cellular and molecular level, and to determine whether or not an understanding of this cell biology phenomenon can be used to explain any of the clinical manifestations of the disease process itself.